Study On Relationship Between Cellular Adhesion Molecule 2(CADM2) And Brain Metastasis In Non-small Cell Lung Cancer

Part 1 Cell adhesion molecule-2 regulates brain metastasis of non-small cell lung cancerObjects:Study the mechanism of NSCLC BMs to provide evidence for the treatment of patients has become an important topic,as Patients with NSCLC BMs have poor prognosis and poor quality of life.Methods:Human transcriptome-wide microarray analysis was used to detect the differential genes between NSCLC with brain metastasis and NSCLC without brain metastasis.More samples were collected and qRT-PCR was used to verify the expression of differential genes in the larger samples.The target gene was transfected into cell modeling with siRNA or oeRNA.The migration and invasion ability of A549 and H322 cells transfected with siRNA or oeRNA were detected by scratch and transwell assay.The expression of epithelial mesenchymal transition related proteins was detected by western blot assay.The brain metastasis of mice inoculated with A549 cells with high expression of CADM2 was detected.Transwell assay was used to detect the effect of interference with MYC expression on the invasion ability of cells with high expression of CADM2.Results:Compared with NSCLC patients without brain metastasis,675 up-regulated genes and 569 down-regulated genes were found in NSCLC plus brain metastasis patients.The result of qRT-PCR showed that CADM2 was significantly upregulated in NSCLC patients with brain metastasis than in those without brain metastasis,which was consistent with the microarray result.CADM2 expression in A549 and H322 cells was silenced by siCADM2 transfection,while CADM2 expression in A549 and H322 cells was increased by oeCADM2 transfection.When the expression of CADM2 was decreased,the cell migration and invasion ability were decreased,and the expression of Vimentin protein was significantly decreased,while the expression of E-cadherin protein was increased.When the expression of CADM2 was increased,the cell migration and invasion ability were increased,and the expression of Vimentin protein was significantly increased,while the expression of E-cadherin protein was decreased.The brain metastasis rate of mice inoculated with A549 cells highly expressed by CADM2 was high.After interfering with MYC expression,the invasiveness of CAM2-overexpressing cells was decreased.Conclusions:1.CADM2 is highly expressed in brain metastases from NSCLC.2.CADM2 can promote the migration and invasion of non-small cell lung cancer cell lines.3.CADM2 can promote brain metastasis in non-small cell lung cancer.4.CADM2 may regulate brain metastasis in non-small cell lung cancer through MYC.Part 2 Effect of cell adhesion molecule-2 on prognosis and clinical factors in non-small cell lung cancer patients with brain metastasisObjects:To analysis the effect of CADM2 on prognosis and clinical factors of non-small cell lung cancer(NSCLC)patients with brain metastases.Methods:Case data and clinical samples of NSCLC patients with brain metastases from January 2015 to December 2017 in Cancer Hospital Affiliated to Guangzhou Medical University were collected.The expression of CADM2 was detected by qRT-PCR.The patients were followed up and the overall survival time was calculated.The influence of CADM2 on overall survival time and clinical factors was analyzed statistically.Results:139 patients with brain metastases from NSCLC were included.The result of x2 test analysis showed that CADM2 gene expression level was not significantly related to gender,age,tumor location,histology,tumor T stage,presence or absence of extracerebral metastasis and smoking(P>0.05).However,it was related to N stage of lymph node metastasis.The higher the expression of CADM2 gene,the higher the N stage of lymph node,and the difference was statistically significant(P<0.05).The result of Log-Rank test showed that there was statistically difference(P<0.05)in the survival time between CADM2 high expression group and CADM2 low expression group.The high expression of CADM2 was correlated with poor prognosis.The result of univariate COX regression analysis showed that age(P=0.031)and CADM2 expression level(P=0.026)were significantly related to survival time,while gender,tumor location,histology,tumor T stage,lymph node N stage,extrabrain metastasis and smoking were not related to survival time.Multivariate COX regression analysis of age and CADM2 expression level showed that CADM2 was an independent risk factor for survival in NSCLC patients with brain metastases(P<0.05).Conclusions:1.The expression of CADM2 is related to N stage of lymph node in NSCLC patients with brain metastasis.The high expression of CADM2 indicates the possibility of lymph node metastasis.2.High expression of CADM2 is associated with poor prognosis of NSCLC patients with brain metastasis,and CADM2 is an independent risk factor for survival of NSCLC patients with brain metastasis.